The immune system is composed of many interdependent cell types that collectively protect the body from bacterial, parasitic, fungal, viral infections and from the growth of tumor cells. Many of these cell types, such a B cells, macrophages, an Natural Killer cells, have specialized functions. The cells of the immune system can engulf bacteria, kill parasites or tumor cells, or kill viral-infected cells. Often, these cells depend on the T helper subset for activation signals in the form of secretions formally known as cytokines, lymphokines, or more specifically interleukins.
Cells of the immune system recognize and are activated by conserved pathogen associated molecular patterns (PAMPs) in infectious agents. The unmethylated CpG dimers embedded in bacterial DNA, as well as certain synthetic oligodeoxynucleotides (ODNs) containing unmethylated CpG sequences (termed a CpG motif) that emulated them, are more frequent in the genomes of bacteria and viruses than vertebrates. Recent studies suggest that immune recognition of these motifs may contribute to the host's innate immune response (Klinman et al., Proc. Natl. Acad. Sci. USA 93: 2879, 1996; Yi et al., J. Immun. 157: 5394, 1996; Liang et al., J. Clin. Invest. 98:1119, 1996; Krieg et al., Nature 374: 546, 1995).
In mice, CpG DNA induces proliferation in almost all (>95%) of B cells and increases immunoglobulin (Ig) secretion. This B-cell activation by CpG DNA is T-cell independent and antigen non-specific. In addition to its direct effects on B cells, CpG DNA has also been shown to activate cells of the immune system (see, for example, International Patent Applications WO 95/26204, WO 96/02555, WO 98/11211, WO 98/18810, WO 98/37919, WO 98/40100, WO 98/52581, PCT/US98/047703, and PCT/US99/07335; U.S. Pat. No. 5,663,153).
However, in many situations, there is a need to suppress an immune response. For example, in an autoimmune disease, a foreign antigen mimics one or more self-proteins, and the immune system produces a response in which a tissue is consequently injured. Similarly, when a subject is the recipient of a transplanted tissue (e.g. a heart, lung, pancreas, or kidney recipient), the body can produce an immune response against the donor tissue. In this situation, there is a clear need to suppress the immune response, in order to avoid rejection of the graft. Additionally, there is a need to suppress the immune response in order to prevent or treat allergic disorders such as asthma.
In view of the above, there exists a need for agents that suppress immune responses. Specifically, there is a need for agents that can be used to suppress the inflammation, and that can be used to suppress an the immune response associated with autoimmune diseases, allergies, and transplant rejection.